Functional Organization of the S-cerevisiae Phosphorylation Network

被引：197

作者：

Fiedler, Dorothea ^{[1
,2
]}

Braberg, Hannes ^{[1
,3
]}

Mehta, Monika ^{[4
]}

Chechik, Gal ^{[5
]}

Cagney, Gerard ^{[1
,3
,6
]}

Mukherjee, Paromita ^{[4
]}

Silva, Andrea C. ^{[4
]}

Shales, Michael ^{[1
,3
]}

Collins, Sean R. ^{[1
,2
,3
]}

van Wageningen, Sake ^{[7
]}

Kemmeren, Patrick ^{[7
]}

Holstege, Frank C. P. ^{[7
]}

Weissman, Jonathan S. ^{[1
,2
,3
]}

Keogh, Michael-Christopher ^{[4
]}

Koller, Daphne ^{[5
]}

Shokat, Kevan M. ^{[1
,2
]}

Krogan, Nevan J. ^{[1
,3
]}

机构：

[1] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, San Francisco, CA 94158 USA

[4] Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA

[5] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

[6] Univ Coll Dublin, Conway Inst, Dublin 4, Ireland

[7] Univ Med Ctr Utrect, Dept Physiol Chem, Utrecht, Netherlands

来源：

CELL | 2009年 / 136卷 / 05期

基金：

美国国家科学基金会;

关键词：

H2A VARIANT HTZ1; PROTEIN-KINASES; TRANSCRIPTION ELONGATION; SIGNALING PATHWAYS; GENETIC-ANALYSIS; IN-VIVO; YEAST; PHOSPHATASE; COMPLEX; ROLES;

D O I：

10.1016/j.cell.2008.12.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Reversible protein phosphorylation is a signaling mechanism involved in all cellular processes. To create a systems view of the signaling apparatus in budding yeast, we generated an epistatic miniarray profile (E-MAP) comprised of 100,000 pairwise, quantitative genetic interactions, including virtually all protein and small-molecule kinases and phosphatases as well as key cellular regulators. Quantitative genetic interaction mapping reveals factors working in compensatory pathways (negative genetic interactions) or those operating in linear pathways (positive genetic interactions). We found an enrichment of positive genetic interactions between kinases, phosphatases, and their substrates. In addition, we assembled a higher-order map from sets of three genes that display strong interactions with one another: triplets enriched for functional connectivity. The resulting network view provides insights into signaling pathway regulation and reveals a link between the cell-cycle kinase, Cak1, the Fus3 MAP kinase, and a pathway that regulates chromatin integrity during transcription by RNA polymerase II.

引用

页码：952 / 963

页数：12

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